Influence of alpha-escin on skeletal changes in ovariectomized rats

The aim of the present study is to investigate the influence of alpha-escin (35 mg/kg per os daily; administered for 4 weeks) on the development of osteopenia caused by bilateral ovariectomy in 3-month-old female Wistar rats. The experiments were carried out on four groups of animals: I (C)--control sham operated rats, II (OVX)--ovariectomized rats, III (E)--sham operated rats which were administered alpha-escin, IV (OVX + E)--ovariectomized rats which were given alpha-escin. In all groups body weight growth, masses, length and tibia diameter were determined as well as histological specimens of right femur and tibia slices were used for histometric measurements including: the transverse cross-section area of the tibial shaft cortex, transverse cross-section area of the tibial marrow cavity, periosteal osteoid width, endosteal osteoid width, periosteal thickness growth in the tibia, endosteal thickness growth in the tibia, epiphyseal and metaphyseal trabeculae thickness in the femur and epiphyseal cartilage width. Bilateral ovariectomy in matured female rats caused osteopenic skeletal changes. alpha-Escin (35 mg/kg per os daily) administered to the ovariectomized rats for the following 28 days decreased only a little the development of osteopenic skeletal changes caused by bilateral ovariectomy.     

Effect of concurrent administration of alendronate sodium and retinol on development of changes in histomorphometric parameters of bones induced by ovariectomy in rats

Retinol is a commonly used vitamin, especially by elderly people. Alendronate sodium, an aminobisphosphonate, is a potent antiresorptive drug used in the treatment of osteoporosis in postmenopausal women. Frequently, alendronate sodium and retinol are used concurrently. There are no reports on the interaction between alendronate sodium and retinol. The aim of the present study was to investigate the effect of concurrent administration of alendronate sodium and retinol on bone remodeling in ovariectomized rats. The histomorphometric parameters of long bones were studied. The experiments were carried out on 3-month-old Wistar rats, divided into 7 groups: I (C) - sham operated control rats, II (OVX) - ovariectomized control rats, III (OVX + ALN) - ovariectomized rats + alendronate sodium (3 mg/kg po), IV (OVX + R-1) - ovariectomized rats + retinol (700 IU/kg po), V (OVX + R-2) - ovariectomized rats + retinol (3500 IU/kg po), VI (OVX + ALN + R-1) - ovariectomized rats + alendronate sodium (3 mg/kg po) + retinol (700 IU/kg po), VII (OVX + ALN + R-2) - ovariectomized rats + alendronate sodium (3 mg/kg po) + retinol (3500 IU/kg po). The drugs were administered to the rats daily by oral gavage (alendronate sodium in the morning, retinol in the afternoon) for 28 days. Body mass gain, bone mass, mineral content in the tibia, femur and L-4 vertebra, histomorphometric parameters of the right tibia (width of osteoid, periosteal and endosteal transverse growth, area of the transverse cross section of the bone marrow cavity and the cortical bone) and the right femur (width of epiphyseal and metaphyseal trabeculae, width of epiphyseal cartilage) were studied. Bilateral ovariectomy induced osteopenic skeletal changes in mature female rats. Alendronate sodium administered at a dose of 3 mg/kg po daily inhibited the development of changes induced by ovariectomy in the skeletal system of rats. Retinol, especially administered at the dose of 3500 IU/kg daily, intensified the changes in the osseous system caused by estrogen deficiency in rats. Retinol administered concurrently with alendronate sodium attenuated the antiresorptive effect of alendronate sodium on the skeletal system in ovariectomized rats.     

Effects of simvastatin on the development of osteopenia caused by ovariectomy in rats

Simvastatin is a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-determining enzyme for cholesterol synthesis which is used in the treatment of hypercholesterolemias, particularly in type IIa and IIb hyperlipoproteinemias, frequently in postmenopausal women. Inhibition of cholesterol synthesis by simvastatin may cause disorders of bone remodelling. The aim of the present study was to investigate the effects of simvastatin (3 mg and 6 mg/kg/day per os) administered for 4 weeks on the development of ovariectomy-induced osteopenia in 3-month-old female Wistar rats. The experiments were carried out on six groups of animals: I (C)--sham operated rats, II (S-3)--sham operated rats + simvastatin 3 mg/kg/day p.o., III (S-6)--sham operated rats + simvastatin 6 mg/kg/day p.o., IV (OVX)--ovariectomized rats, V (OVX + S-3)--ovariectomized rats + simvastatin 3 mg/kg/day p.o., VI (OVX + S-6)--ovariectomized rats + simvastatin 6 mg/kg/day p.o. In all the groups, we examined body weight gain, and macrometrical, histomorphometrical and mechanical parameters. Bilateral ovariectomy induced osteopenic skeletal changes in mature female rats. In cortical bone, ovariectomy intensified resorption processes at the marrow cavity, as indicated by a decrease in endosteal transverse growth and an increase in transverse cross-section surface area of the marrow cavity in the tibia. Intensification of resorption processes was observed in cancellous bone (a statistically significant decrease in the width of trabeculae in the epiphysis and metaphysis of the femur). Structural changes in the long bones resulting from bilateral ovariectomy were manifested by deterioration of mechanical properties of the shaft and neck of the femur. The force needed to fracture the neck and shaft of the femur was significantly smaller than that in sham operated rats. Simvastatin (3 and 6 mg/kg/day p.o.) slightly influenced bone remodelling in sham operated rats. Simvastatin (3 and 6 mg/kg p.o. daily) administered to ovariectomized rats intensified bone formation processes and decreased bone resorption processes induced by bilateral ovariectomy, showing stronger activity at 6 mg/kg.     

Influence of alpha-escin on the femoral bone strength in ovariectomized rats

The aim of the present study was to investigate the effect of alpha-escin (35 mg/kg po, daily) administered for 4 weeks on the femoral bone strength in 3-month-old ovariectomized Wistar rats. The experiments were carried out on four groups of animals: I (C)-control sham operated rats, II (OVX)-ovariectomized rats, III (E)-sham operated rats which were administered alpha-escin, IV (OVX+E)-ovariectomized rats which were administered alpha-escin. Bilateral ovariectomy caused osteopenic skeletal changes in mature female rats. alpha-Escin (35 mg/kg po, daily) administered to the ovariectomized rats for 28 days only to little extent decreased the development of osteopenic skeletal changes which were caused by bilateral ovariectomy. alpha-Escin (35 mg/kg po, daily) administered to the sham operated rats for 28 days caused slight changes in the skeletal system, which were characterized by the increase in the bone formation processes.     

Effect of administration of alendronate sodium and retinol on the mechanical properties of the femur in ovariectomized rats

Alendronate sodium, an aminobisphosphonate with potent antiresorptive activity, is used in the treatment of postmenopausal osteoporosis. Retinol, as a component of multivitamin preparations, is frequently used especially by elderly people. There are no reports on the interaction of alendronate sodium and retinol. The aim of the present study was to investigate the effect of administration of alendronate sodium and retinol on mechanical properties of the femoral bone in bilaterally ovariectomized rats. The experiments were carried out on 3-month-old Wistar rats, divided into 7 groups: I - sham-operated control rats, II - ovariectomized control rats, III - ovariectomy + alendronate sodium 3 mg/kg po, IV - ovariectomy + retinol 700 IU/kg po, V - ovariectomy + retinol 3500 IU/kg po, VI - ovariectomy + alendronate sodium 3 mg/kg po + retinol 700 IU/kg po, VII - ovariectomy + alendronate sodium 3 mg/kg po + retinol 3500 IU/kg po. The drugs were administered to the rats daily by oral gavage for 28 days. Body mass gain, bone mass, bone mineral content and calcium content in the femur and L-4 vertebra and mechanical properties of the whole femur (extrinsic stiffness, ultimate load, breaking load, deformation caused by the ultimate load) and the neck of the femur (load at fracture), were examined. Bilateral ovariectomy induced osteopenic changes in the rat skeletal system. Alendronate sodium (3 mg/kg po) counteracted the development of osteopenia induced by ovariectomy. Retinol at both used doses unfavorably affected the examined bone parameters of ovariectomized rats. Retinol administered with alendronate sodium lessened the preventive action of alendronate on the development of osteopenic changes in the skeletal system of ovariectomized rats.     

Effects of retinol on development of osteopenic changes induced by bilateral ovariectomy in rats

Skeletal disorders occurring in experimental model of osteopenia caused by bilateral ovariectomy in rats are similar to those observed in postmenopausal women. Retinol is a commonly used vitamin, especially by elderly people. The role of retinol in bone remodeling is not well-established. The aim of the present study was to investigate the effect of retinol administered at doses of 700 IU/kg p.o. daily and 3500 IU/kg p.o. daily for 28 days on the development of osteopenia induced by bilateral ovariectomy in 3-month-old Wistar rats. The experiments were carried out on 4 groups of animals: I (C)--sham-operated control rats, II (OVX)--ovariectomized control rats, III (OVX + R700)--OVX rats treated with retinol (700 IU/kg p.o. daily), IV (OVX + R3500)--OVX rats treated with retinol (3500 IU/kg p.o. daily). Body mass gain, bone mass, mineral and calcium content in the tibia, femur and L-4 vertebra, histomorphometric parameters of the right tibia (width of osteoid, periosteal and endosteal transverse growth, the area of the transverse cross section of the bone marrow and cortical bone) and the right femur (width of epiphyseal and metaphyseal trabeculae, width of epiphyseal cartilage), and mechanical properties of the femur were investigated. Bilateral ovariectomy induced osteopenic skeletal changes in mature female rats. Retinol at doses of 700 IU/kg p.o. daily and 3500 IU/kg p.o. daily decreased bone mass (statistically significantly after treatment with 3500 IU/kg p.o. daily). Retinol at both doses caused statistically significant increases in the width of periosteal osteoid, and, at a dose of 3500 IU/kg p.o. daily, of endosteal osteoid. The increase in the width of osteoid may be the effect of disorder of its mineralization, as the decreases in bone mineral and calcium content were also noted. In mechanical tests of the femur, dose-dependent decreases in the ultimate load, the breaking load and the deformation caused by the applied load were observed after administration of retinol (in comparison with the OVX control rats). Concluding, retinol (especially administered at the dose of 3500 IU/kg daily) intensified the changes in the osseous system caused by estrogen deficiency in rats.     

Effects of doxycycline on development of changes in histomorphometric parameters of bones induced by bilateral ovariectomy in rats

Tetracyclines are considered potential medication for the treatment of osteoporosis. The aim of the present study was to investigate the effects of doxycycline on development of unfavorable changes in bone histomorphometric parameters induced by bilateral ovariectomy in rats. Doxycycline at a dose of 20 mg/kg po daily was administered for 28 days to bilaterally ovariectomized and sham-operated 3-month-old Wistar rats. Bone histomorphometric parameters of the tibia (transverse growth, width of periosteal and endosteal osteoid, area of the transverse cross-section of the diaphysis and area of the transverse cross-section of the marrow cavity) and the femur (width of epiphyseal and metaphyseal trabeculae, width of epiphyseal cartilage) were examined. Bilateral ovariectomy caused symptoms of osteopenia in the rat bones. Doxycycline counteracted the unfavorable changes in bone structure caused by estrogen deficiency. However, in the sham-operated rats doxycycline itself induced deleterious effects in the trabecular bone.     

Bone remodeling after administration of proton pump (H+/K+-ATPase) inhibitors and alendronate in ovariectomized rats

During osteoporosis therapy with alendronate, esophagitis and stomach ulceration may occur, requiring the concurrent use of drugs which decrease gastric juice production. The aim of the present study was to investigate the effect of concurrent administration of proton pump (H+/K+ATP-ase) inhibitors: omeprazole or pantoprazole and alendronate on bone remodeling in ovariectomized rats. The experiments were carried out on 3-month-old Wistar rats, divided into following groups (n = 8-10): NOVX - non-ovariectomized control rats; OVX - ovariectomized control rats; OVX + alendronate; OVX + omeprazole; OVX + omeprazole + alendronate; OVX + pantoprazole; OVX + pantoprazole + alendronate. The drugs were administered for 28 days: alendronate (3 mg/kg p.o.), omeprazole or pantoprazole (3 mg/kg i.p.). Bone remodeling was estimated based on histomorphometric evaluation of the tibia (endosteal and periosteal transverse growth and the osteoid width, transverse cross-section surface of the diaphysis and of the marrow cavity) and the femur (width of trabeculae in the distal epiphysis and metaphysis). Bone mass/100 g body mass and mass of bone mineral/100 mg bone mass in the tibia and femur were also determined. Pantoprazole stronger than omeprazole intensified bone remodeling disorders caused by estrogen deficiency in ovariectomized rats. Bone remodeling disorders were the result of intensification of bone resorption with concurrent inhibition of bone formation and mineralization. Pantoprazole, and to lesser extent omeprazole, weakened the preventive effect of alendronate on bone remodeling in ovariectomized rats.     

Effect of administration of retinol and etidronate on bone histomorphometric parameters in ovariectomized rats

Retinol belongs to factors affecting bone remodeling. The effect of retinol on the osseous tissue depends on the dose and duration of treatment. Retinol can cause bone damage and deformation. Retinol is frequently administered chronically in too high doses, sometimes by osteoporotic patients. The aim of the present study was to examine the interaction between retinol and an antiresorptive drug--disodium etidronate in bilaterally ovariectomized rats. The experiments were carried out on Wistar rats (200 +/- 30 g), divided into 7 groups: I--sham operated control rats. II--ovariectomized control rats (OVX), III--OVX + editronate (10 mg/kg p.o.), IV--OVX + retinol (700 IU/kg p.o.). V--OVX + retinol (3500) IU/kg p.o.), VI--OVX + etidronate (10 mg/kg p.o.) + retinol (700 IU/kg p.o.), VII--OVX + etidronate (10 mg/kg p.o.) + retinol (3500 IU/kg p.o.). The drugs were administered for 4 weeks. Bone macrometric and histomorphometric parameters of the tibia (transverse growth, width of periosteal and endosteal osteoid, area of the transverse cross-section of the diaphysis and area of the transverse cross-section of the marrow cavity) and the femur (width of epiphyseal and metaphyseal trabeculae, width of epiphyseal cartilage) were examined. Editronate partially counteracted the development of changes induced by ovariectomy. Retinol (700 IU/kg p.o.) caused decreases in the area of the transverse cross-section of the marrow cavity and the width of osteoid, and an increase in the width of trabeculae. Retinol (3500 IU/kg p.o.) caused decreases in bone mass and the area of the transverse corss-section of the marrow cavity, and an increase in the width of trabecula. Concurrent administration of etidronate and retinol in ovariectomized rats seemed not to affect bone histomorphometric parameters in a way suggesting any interaction between them.     

Effects of diphenyl diselenide on lipid profile and hepatic oxidative stress parameters in ovariectomized female rats

Objectives Ovarian hormone decline after menopause is linked to many pathophysiological reactions. Female rats submitted to ovariectomy are employed as a model of post‐menopausal condition. This study investigated the effects of diphenyl diselenide (PhSe)₂ on body weight gain, intra‐abdominal fat deposition, plasma lipid profile and hepatic oxidative stress in ovariectomized rats. Methods Female adult Wistar rats were ovariectomized (OVX rats) or sham‐operated and divided into four groups: (i) sham‐operated, (ii) (PhSe)₂, (iii) OVX and (iv) OVX + (PhSe)₂. (PhSe)₂ (5 mg/kg; 5 ml/kg, p.o.) was administered once a day for 30 days to groups (ii) and (iv). After that, rats were anaesthetized for blood sample gathering and submitted to euthanasia. Key findings (PhSe)₂ (5 mg/kg) was effective in preventing the rise in body weight gain and intra‐abdominal fat deposition induced in OVX rats. Although (PhSe)₂ was not effective in avoiding the increase in plasma total cholesterol and non‐HDL levels induced in OVX rats, (PhSe)₂ reduced plasma triglycerides and augmented HDL levels in OVX rats. (PhSe)₂ also increased hepatic ascorbic acid levels, reduced glutathione content, glutathione S‐transferase activity and restored catalase activity in liver of OVX rats. Conclusions These findings suggest that (PhSe)₂ could be a promising alternative to minimize menopause related symptoms.     

黄柏小檗碱对去卵巢大鼠骨质疏松症的作用

目的：研究黄柏小檗碱对去卵巢大鼠骨质疏松症的作用.方法：去卵巢以建立大鼠骨质疏松症模型,将大鼠随机分为假手术组、去卵巢组,尼尔雌醇组及低（10 mg/kg）、中（30 mg/kg）、高（90 mg/kg）剂量黄柏小檗碱组进行实验,每组10只.12周后,以比色法测定其血清钙、磷的浓度和碱性磷酸酶的活性,竞争放射免疫法测定血清中骨钙素、降钙素、甲状旁腺素及雌二醇的浓度;双能X射线骨密度仪测定大鼠股骨干骺端的骨密度.结果：黄柏小檗碱能够增加去卵巢大鼠子宫重量、股骨干骺端的骨密度和血清无机磷含量;降低碱性磷酸酶活性和甲状旁腺素浓度,增加血清雌二醇、骨钙素、降钙素浓度.结论：黄柏小檗碱对去卵巢大鼠骨质疏松症具有防治作用,其机制可能是抑制骨吸收、促进骨形成,促进雌二醇和降钙素合成.     

Ameliorative effects of <Emphasis Type="Italic">Vaccaria segetalis</Emphasis> extract on osteopenia in ovariectomized rats

The purpose of this study was to determine the ameliorative effects of a crude extract of Vaccaria segetalis (Neck.) Garcke (Caryophyllaceae) (VSE) on osteopenia in ovariectomized (OVX) rats over 12 weeks. Rats were divided into the sham and OVX groups. The OVX rats were allowed to lose bone for 6 weeks. At 6 weeks post-OVX, the OVX rats were divided into four groups treated with water, 17β-estradiol (30 μg/kg, daily subcutaneous injection), or VSE (0.5 or 1.0 g/kg, daily, orally) for 6 weeks. In OVX rats, the increases of serum total cholesterol were significantly decreased by VSE or 17β-estradiol treatment. There were decreases in bone density and calcium content, including the left femur and the fourth lumbar vertebra, when compared with the sham control rats. Treatment with 17β-estradiol or VSE ameliorated these changes induced by OVX. In addition, ovariectomy increased urinary deoxypyridinoline (DPD) amounts (P < 0.001). The increases were suppressed by 17β-estradiol and 0.5 or 1.0 g/kg VSE (P < 0.01, P < 0.05, P < 0.01, respectively). Our results demonstrated that VSE ameliorates ovariectomy-induced osteopenia by inhibition of bone resorption.     

大豆异黄酮对去卵巢大鼠骨密度和雌激素活性的影响(英文)

目的 :研究大豆异黄酮对去卵巢大鼠骨密度以及雌激素活性的影响。方法 :将 10～ 12月龄的雌性Wistar大鼠随机分为 6组 :假手术组 (SHAM )、切卵巢模型组 (OVX)、尼尔雌醇组 (OVX E)、小剂量异黄酮组 (L ISO)、中剂量异黄酮组 (M ISO)、大剂量异黄酮组 (H ISO) ,每组 8只。后 5组大鼠被切除双侧卵巢 ,SHAM组只被切除卵巢附近脂肪组织。L ISO ,M ISO ,H ISO分别灌胃给予 30 ,6 0 ,12 0mg·kg- 1的大豆异黄酮 ,OVX E组大鼠灌胃给予0 .2mg·kg- 1·wk- 1的尼尔雌醇 ,SHAM与OVX组以等剂量的溶剂灌胃 ,15wk后股动脉放血处死动物 ,收集血液用于血清碱性磷酸酶活性、血清雌二醇水平、血钙、血磷测定 ,分离出右侧股骨、第 2腰椎用于骨密度测量 ,测定双侧子宫重量。结果 :与SHAM组相比 ,OVX组股骨骨密度和椎骨骨密度均可见不同程度降低 (P <0 .0 5和P >0 .0 5 ) ,尼尔雌醇与异黄酮 12 0mg·kg- 1能明显升高去卵巢大鼠的股骨和椎骨骨密度 (P <0 .0 5 )。OVX组的血清碱性磷酸酶水平高于SHAM组 (P <0 .0 5 ) ,异黄酮6 0mg·kg- 1可降低去卵巢大鼠的血清碱性磷酸酶水平 (P <0 .0 5 )。OVX组的血清雌二醇水平与子宫系数明显低于SHAM组 (P <0 .0 1) ,异黄酮的不同剂量组与OVX E组的血清雌二醇水平、子宫系数都明显高于OV     

Preventive effect of Peperomia pellucida (L.) Kunth herbs on ovariectomy-induced osteoporotic rats

Osteoporosis is a metabolic skeletal disorder leading to bone fracture which adversely impacts the quality of life. In the present, we aimed to investigate the effect of Peperomia pellucida (L.) Kunth herb juice and ethanolic extract on ovariectomy (OVX)-induced osteoporotic rat model. Osteoporosis was induced by OVX with a double dorsolateral approach on female Wistar rats. Female Wistar rats undergoing sham surgeries (sham-control group) served as controls. The ovariectomized rats were divided into six groups based on administered treatments, (i) CMC Na 0.3% (OVX-control group), (ii) standard drug (ethynil estradiol 4.5 µg/kg), (iii) P. pellucida juice at dose of 50 mg/kg, and (iv) 100 mg/kg, (v) P. pellucida ethanolic extract at dose of 50 mg/kg, and (vi) 100 mg/kg. Treatments were started 1 week after the surgeries and lasted for 6 weeks. Rats treated with 100 mg/kgP. pellucida ethanol extract had significantly decreased serum ALP level and reduced excretion of urine calcium compared with the OVX-control group (P<0.05). These levels were not significantly altered when compared with the sham-control group (P<0.05). Furthermore, 100 mg/kg ethanolic extract-treated group showed improvement on three-dimensional image of the trabecular bone compared with the OVX-control group. Trabecular cavity formation in 100 mg/kg ethanolic extract-treated group was minimal. Ethanolic extract of Peperomia pellucida (L.) Kunthherbs at a dose of 100 mg/kg had preventive effect on OVX-induced osteoporotic rats.     

Effects of alpha-escin on histomorphometrical parameters of long bones in rats with experimental post-steroid osteopenia

The excess of glucocorticosteroids leads to the development of osteopenia. A decreased bone formation rate and an increased bone resorption rate are observed. The aim of the present study was to investigate the effects of alpha-escin on the experimental prednisolone-induced osteopenia. The experiments were carried out on male Wistar rats with initial body weight of 240-310 g, divided into 4 groups (n = 6): Control, Alpha-escin, Prednisolone, Prednisolone + alpha-escin. Prednisolone (5 mg/kg im daily) and/or alpha-escin (100 mg/kg po daily) were administered for 28 days. Transverse cross-section surfaces of the cortical diaphysis and of the marrow cavity in the tibia, transverse growth, width of endosteal and periosteal osteoid, thickness of trabeculae and width of epiphyseal cartilage were examined. Prednisolone administration caused osteopenic changes in rat bones. Alpha-escin administered to the control rats did not exert statistically significant influence on the investigated bone parameters. Alpha-escin administration to prednisolone-treated rats slightly reduced the unfavorable effects of prednisolone on width of periosteal and endosteal osteoid and periosteal transverse growth in the tibia.     

Effects of D-003, a mixture of high molecular weight aliphatic acids from sugar cane wax, on bones from ovariectomized rats

Bisphosphonates inhibit bone resorption through mechanisms involving the metabolic pathway from mevalonate to cholesterol. Mevalonate is a precursor of the lipoids required for osteoclast activity and thus inhibition of its synthesis affects bone metabolism. Inhibitors of hydroxymethylglutaryl CoA (HMGCoA) reductase might increase experimentally new bone formation through a mevalonate-dependent effect. D-003 is a mixture of high molecular weight fatty acids isolated from sugar cane wax, which inhibits cholesterol biosynthesis through indirect regulation of HMGCoA reductase activity. This study was undertaken to determine whether D-003 could prevent bone loss in ovariectomized rats. Sprague Dawley female rats were ovariectomized or sham operated and were randomly distributed into five groups: a control ovariectomized and a sham (false-operated) group receiving Tween/H2O vehicle, a group treated with alendronate (3 mg/kg/day) and two groups treated with D-003 (50 and 200 mg/kg/day). Treatments were administered for 3 months. At sacrifice, bones were removed and histological variables of bone resorption and formation were studied by histomorphometry. Ovariectomy diminished trabecular number and thickness and increased trabecular gap, osteoclast number and surface. Alendronate and D-003 prevented a decrease in trabecular number and thickness as well as increases in trabecular separation, osteoclast number and surface compared with ovariectomized controls, thus preventing the bone loss and decreased bone resorption induced by ovariectomy, but failed to increase osteoblast surface compared with control ovariectomized rats. In conclusion, D-003 (50 and 200 mg/kg/day) prevented bone loss and decreased bone resorption in ovariectomized rats, which suggests that this substance could be promising in preventing or treating osteoporosis.     

Bone loss preventing effect of sophorae fructus on ovariectomized rats

The preventive effects of Sophorae Fructus extracts (I: hot water extract and II: combination product using I) on bone loss in ovariectomized (OVX) rats were investigated. Sophorae Fructus extracts were orally administrated to OVX rats for 9 weeks. Ovariectomy caused the increase of body weight and deoxypyridinoline (Dpd: bone resorption marker) and decrease of calcium (Ca: bone formation marker) level in serum. Dpd level were significantly decreased and Ca levels were elevated at 9 weeks in Sophorae Fructus extracts administered groups after ovariectomy at a dose of 0.556 g/kg/day compared with control group. In administered groups, trabecular bone area (TBA) in the tibia and lumbar were also increased compared with control group in histomorphological analysis. The preventive or treatment effects of Sophorae Fructus extracts on bone loss in OVX rats appears to be due to suppression of bone turnover.     

Glucocorticoid-induced secondary osteopenia in female rats: a time course study as compared with ovariectomy-induced osteopenia and response to salmon calcitonin

Previously we reported that 8-week treatment with methylprednisolone acetate (MPA: 0.1 mg/kg, s.c., 3 days a week) of male rats caused a novel type of osteopenia whose development was prevented by salmon calcitonin (SCT) in a dose-dependent manner. In this study, to compare the MPA-inducible osteopenia with the ovariectomy (OVX)-inducible one, female rats were used instead of male rats and a time-course study of development was made. MPA treatments for 1, 2, 4 and 8 weeks histologically induced characteristic osteopenic changes in a time-dependent manner that were histomorphometrically detectable in tibiae within 4 weeks as reduced bone mass, accelerated bone resorption, and suppressed bone formation and mineralization. Node-strut analysis revealed that the connectivity of the trabecular structure remained unaffected. Such MPA-induced changes in the trabecular structure, to be defined as thinned-but-uncut, is in a good contrast with OVX-induced unthinned-but-cut structure, although the latter osteopenic changes became detectable 2 weeks earlier. Another previous finding confirmed herein was that MPA-induced osteopenia in female rats was also completely masked by SCT (10 U/kg, s.c., 5 days a week). The results indicate that the MPA-inducible secondary osteopenic model in either sex of rats would be usable for testing anti-osteopenic drugs.     

Effects of osthole on postmenopausal osteoporosis using ovariectomized rats; comparison to the effects of estradiol

The purpose of this study was to examine effects of osthole on postmenopausal osteoporosis using ovariectomized (OVX) rats. All of the rats were divided into sham and OVX groups. At 2 weeks post-operation, the sham-operated rats received solvent vehicle (97% corn oil and 3% ethanol, 1.0 ml/kg, subcutaneously); the OVX rats were divided into three groups which were treated with solvent vehicle (same the sham rats, 1.0 ml/kg, subcutaneously), 17beta-estradiol (30 microg/kg, subcutaneously) or osthole (9.0 mg/kg, orally) 5 d/week for 4 weeks, respectively. In OVX rats, the increases of body weight, spleen and thymus weight were significantly decreased and the atrophy of uterus was preserved by 17beta-estradiol treatment, but not by osthole. Treatment with either 17beta-estradiol or osthole significantly protected cancellous bone loss owing to estrogen deficiency and significantly increased the maximal load in the femoral neck of OVX rats. In addition, the increases of serum osteocalcin (OC) and urinary deoxypyridinoline (DPD) levels caused by ovariectomy were all significantly suppressed by 17beta-estradiol. However, only urinary DPD was significantly reduced by osthole and no change was found in serum OC. Our results demonstrate that osthole may be just as effective as 17beta-estradiol in suppressing bone loss due to ovariectomy but osthole perhaps does not work through the estrogen pathway.     

Effects of doxycycline on the development of bone damage caused by prednisolone in rats

The aim of the present study was to investigate the effects of doxycycline on the development of bone damage caused by prednisolone in rats. The experiments were carried out on male WAG rats (200-260 g), divided into 2 control and 6 experimental groups receiving prednisolone (5 mg/kg im daily) or/and doxycycline (100 mg/kg po daily) for 2 or 4 weeks. The animals were sacrificed on the 15th or 29th day of the experiment and the following characteristics were examined: mass, length, mechanical properties, mineral and calcium content in the tibia and femur, width of endosteal and periosteal osteoid, endosteal and periosteal transverse growth, transverse cross-section area of the diaphysis and of the marrow cavity in the tibia, width of epiphyseal cartilage and width of trabeculae in the femur. Prednisolone caused features of osteopenia (inhibition of bone formation and intensification of bone resorption), which were stronger after 4 weeks of the experiment. Doxycycline administered alone for 2 or 4 weeks intensified the processes of bone formation and resorption. Doxycycline to some degree attenuated the influence of prednisolone on rat bones.